Safety and tolerability concerns accompany the use of vaccines that incorporate live-attenuated or killed microorganisms. Vaccines containing virus particles incapable of replication are desired, e.g., virus-like particles that do not contain DNA or RNA but that are composed of pathogen derived proteins that can illicit an immune response. A drawback of this approach is that some protein-based vaccines lack some of the inherent immunostimulatory properties of whole organism-based vaccines resulting in suboptimal responses. Thus, there is a need to discover improved methods of vaccination.
Adjuvants are compounds typically co-injected with vaccines to boost immune responses. While certain adjuvants can enhance the immune response to some vaccines, they are not always universally effective or applicable to specific routes of immunization. Thus, there is a need to discover improved adjuvants depending on the antigen (vaccine) and route of immunization. For instance, vaccine responses against influenza are not greatly improved with the addition of alum. Alum, an adjuvant used in DTP vaccines, is a skin irritant and not suitable for skin vaccination. Therefore, there is a critical need to discover novel adjuvants that are broadly effective for each antigen and route of vaccination.
Skountzou et al. report transcutaneous immunization with inactivated influenza virus induces protective immune responses. Vaccine, 2006, 24, 6110-6119. See also Koutsonanos et al. Transdermal influenza immunization with vaccine-coated microneedle arrays. PloS one, 2009, 4, e4773. See also U.S. Patent Application Publication Nos 2014/0170299, 2008/0213461, and 2002/0082527.
Pulit-Penaloza et al. report modulation of influenza vaccine immune response using an epidermal growth factor receptor kinase inhibitor. Sci. Rep. 2015, 5, 12321.
Kermeny et al. report dithranol (Anthralin) is effective in the treatment of psoriasis that may exert an immunosuppressive effect. Skin Pharmacol, 1990, 3:1-20. See also Amin et al., J Saudi Soc Dermat & Dermat Surgery, 2013, 17, 37-45; Schopt et al., Immunosuppression by Anthralin, J Invest Dermat, 1996, 106(4) 841; and WO 2011/027222
Adenovirus vaccine utilizing IKK as an adjuvant is reported in US 2009/0202492. See also US 2010/0151000, US 2010/0151000, and US20080124322.
Zhang et al report endocytic mechanisms and toxicity of a functionalized fullerene in human cells. Toxicol Lett. 2009; 191(2-3):149-57. Vaccine adjuvant and vaccine formulations of fullerene derivatives are reported in CN103495164.
U.S. Patent Application Publication No. 2015/0174234 report influenza vaccines with oil-in-water emulsion adjuvants.
References cited herein are not an admission of prior art.